Altered NAD(P)H production in neonatal rat islets resistant to H2O2.
OBJECTIVE
We determined the involvement of NAD(P)H generation ability on the resistance of pancreatic islets B-cells to oxidative stress caused by culture exposition to H2O2.


METHODS
We cultured isolated neonatal Wistar rat islets for four days in medium containing 5.6 or 20 mM glucose, with or without H2O2 (200 microM), and analyzed several parameters associated with islet survival in different media. High glucose was used since it protects neonatal islets against the loss of GSIS.


RESULTS
While none of the culture conditions increased the rate of NAD(P)H content at 16.7 mM glucose, the islets resistant to H2O2 and those exposed to 20 mM glucose showed a greater use of the pentose phosphate pathway and increased ATP synthesis from glucose.


CONCLUSIONS
Oxidative stress contributes to the loss of glucose-induced insulin secretion (GSIS) during the onset of diabetes mellitus. Although immature rat islets have reduced GSIS compared to mature islets, they adapt better to oxidative stress and are a good model for understanding the causes involved in the destruction or survival of islet cells. These data support the idea that GSIS and resistance against oxidative stress in immature islets rely on NADH shuttle activities, with little contribution of reduced equivalents from the tricarboxylic acid cycle (TCAC).
Stoppiglia
Luiz F
LF
Departamento de Química, Instituto de Ciências Exatas e da Terra, Universidade Federal de Cuiabá, MT, Brazil.
Rezende
Luiz F
LF
Cappelli
Ana P G
AP
Ferreira
Fabiano
F
Boschero
Antonio C
AC
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004351:Drug Resistance; D005947:Glucose / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D009249:NADP / Q000096:biosynthesis*; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012402:Rotenone / Q000494:pharmacology; D000637:Transaminases / Q000037:antagonists & inhibitors
D007328:Insulin; D016877:Oxidants; D012402:Rotenone; D009249:NADP; D006861:Hydrogen Peroxide; D000637:Transaminases; D005947:Glucose